PROJECT SUMMARY For more than 60 years, the Gordon Research Conference on Bones & Teeth (B&T GRC) has distinguished itself as a forum for the exchange of cutting-edge ideas on the physiology and pathology of bone, bone-related tissues and teeth (herein referred to as the skeleton). In the past decade, the Gordon Research Seminar (GRS) held one day before the GRC and focused on participation of trainees and early career investigators has promoted close interactions between next-generation scientists and senior investigators. The 2020 B&T GRC and GRS will continue and strengthen this tradition. Through structured scientific presentations, formal and informal discussions, and highly interactive poster sessions held over the course of 6 days (1day GRS plus 5 days GRC), the meetings are designed to showcase the latest scientific discoveries and to catalyze cross-disciplinary collaborations. Despite impressive advances in our understanding of the cellular, molecular and genetic mechanisms governing normal skeletal development and homeostasis, diseases of the skeleton, including osteoporosis, osteoarthritis, fracture repair failure, bone cancer, and periodontitis continue to be major contributors to adult morbidity and mortality. By bringing together experts in signal transduction, extracellular matrix (ECM) biology, stem cell biology, developmental biology, molecular genetics, physiology, endocrinology, aging, and emerging technologies, the 2020 B&T GRC hopes to capture the tremendous momentum and progress in the field, inspire new research directions, and foster new collaborations aimed at advancing therapeutic development in the skeletal arena. The theme of the 2020 B&T GRC is The Life of the Skeleton. Starting with an introduction to signaling circuits, stem cells, and ECM, we examine the events directing skeletal homeostasis in chronological order, and at specific temporal inflection points compare and contrast the appendicular, axial and craniofacial skeletal responses. We also discuss emerging technologies that allow us to investigate skeletal biology in new ways, and end our meeting by focusing on whether repair/regeneration of adult skeletal tissues is a return to principles that govern embryonic skeletal development, or representative of a new stage of skeletal biology, a controversial topic vital to development of successful therapeutic approaches in the adult skeleton. Both the scientific content and the collaborative spirit of the GRC and GRS are directly aligned with the missions of multiple NIH institutes including NICHD, NIDCR, NIA, and NIAMS.